We propose that the establishment of a Rheumatic Diseases Center that will bring together 34 independent investigators of the rheumatic diseases at three neighboring non-profit research institutions: the University of California San Diego (UCSD, The Scripps Research Institute (TSRI), and the La Jolla Institute for Allergy and Immunology (LJIAI). The theme of the Center will be to facilitate translational rheumatology research, assist in fundamental studies of rheumatic disease pathogenesis, and evaluate the effects of novel anti-rheumatic agents with therapeutic potential; and ii) To facilitate and provide technical support for investigator-initiated clinical trials of novel therapeutic approaches. Three core facilities will assist these research activities. The Molecular Biology ore (PI-G.J. Silverman) will facilitate the timely utilization of molecular biology techniques by affiliated physicians and scientists by providing several specialized services. The Biomarker Core techniques by affiliated physicians and scientists by providing several specialized services and instruction in the application of diverse, cutting edge and labor intensive assays of protein and RNA expression that are relevant to animal and clinical investigations. The Animal Genetics Core (PI-M.P Corr) will provide expert services for the in-breeding of murine strains with desirable transgenic and knock out phenotypes on useful well-defined immunologic and metabolic backgrounds. Under the supervision of the Scientific Director (D.A. Carson), the Center will also support two Pilot and Feasibility Projects (P&F): Project 1 (P-S.Liu, TSRI) will develop transgenic murine models to investigate the role of the intracellular signaling adaptor molecule, paxillin, for alpha-4 integrin mediated signaling and the effects of inflammatory cell function and gene expression. Project 2 (PI-L. Leoni, UCSD) will characterize the immunomodulatory activities of small synthetic molecules, termed IBT, on IBT, on IL-4/STAT mediated signaling established murine model of inflammatory arthritis. As part of an ongoing Enrichment Program, the Center will host weekly seminars on clinical immunology, inflammation and arthritis from local and visiting investigators, presenting the latest developments in their fields. To further facilitate investigative collaborations relating to the two central aims of the Center, we will also host two one-day Research Retreats for affiliated investigators. An Administrative Core (PI-G.J. Silverman, Center Director) will provide overall direction and supervision to all Center programs through an Executive Committee, which will be assisted by an Outside Advisory Committee.